More recently, Jiang et al. identified galectin-9 expression as an independent prognostic factor in a retrospective study on 305 patients with gastric cancer. Again, low galectin-9 expression was associated with poor survival. Galectin-9D5 is one of the three most frequently identified galectin-9 variants. These splice AZD2281 company variants encode protein isoforms that vary in the length of the linker region between the two CRD domains which affects multimer formation and valency. Previous data suggest that the different galectin-9 isoforms have a diverging role in tumor cells, e.g. they differently affect the adhesion of cells to the ECM and to the endothelium. In general, altered galectin-9 expression has been linked to abnormal cell adhesion, growth and migration. Others have described that galectin-9 can influence cell survival as well as homo- and heterotypic cell aggregation. Loss of galectin-9 expression could compromise tissue integrity allowing tumor cells to intravasate into circulation and metastasize. Indeed, in breast cancer low galectin-9 expression was a better predictor of distant metastasis compared to lymph node status. Similar observations were made in melanoma and cervical squamous cell carcinoma. However, these effects depend on multiple parameters, including the specific galectin-9 variant, the type of cell and the adhesion matrix component to which the cells bind. Whether and how all these parameters influence lung cancer progression requires further studies. Possibly, galectin-9 can act as a chemoattractant for lung cancer cells, similar as described for eosinophils or endothelial cells. Together with our observation that stromal galectin-9D5 expression remains elevated in lung tumors this chemoattracting activity indicates that galectin9D5 might act as a guidance cue for metastatic tumor cells to migrate towards the site of intravasation, i.e. the vasculature. This could promote tumor metastasis especially if loss of galectin-9 in tumor cells results in loss of tissue integrity. Finally, it has been reported that in animal models and cancer patients, tumor cells can release galectin-9 containing exosomes that can induce Tcell apoptosis. Whether tumor endothelial cells also secrete galectin-9 containing exosomes needs to be further investigated, but such a mechanism could contribute to tumor progression by providing a way to escape immune surveillance. Immunohistochemical assessment of galectin-1 and galectin-9 protein expression showed differences in the localization and distribution within the tumor tissue. These observations are in line with previous findings in different tumors where both galectin-1 and galectin-9 proteins could be detected in different compartments of the tumor, including tumor cells, tumor stroma and tumor endothelial cells. Nevertheless, protein expression had no prognostic value in our patient group. Most likely, this is related to the fact that immunohistochemical staining represents a more qualitative evaluation rather than a quantitative analysis. Thus, actual protein expression levels could not be accurately quantified by IHC staining.